The sweetener L-aspartyl-L-phenylalanine methyl ester (Formula 1) is known to be about 180 times sweeter than sucrose, weight to weight. Other peptides with increased sweetening power are also known to the art. See, for example, R. H. Mazur et al., J. Am. Chem. Soc. 91:2684-2691 (1969); Zanno et al., U.S. Pat. Nos. 4,572,799; Zanno et al., 4,571,308; Zanno et al., 4,603,012; H. Iwamura, J. Med. Chem. 24:572-583 (1981); L. B. P. Brussel et al., Z. Lebensm. Untersuch.-Forsch. 159:337-343 (1975); Y. Miyashita et al., J. Med. Chem. 29:906-912 (1986); Tsang et al., J. Med. Chem. 27:1663-1668 (1984); R. H. Mazur et al., J. Med. Chem. 16:1284 (1973); W. Grosch et al., Naturwissenschaften 64:335 (1977); Sheehan et al., U.S. Pat. No. 3,978,034. ##STR2##
One compound discovered as a result of the research for high intensity sweeteners is L-aspartyl-2-amino malonyl methyl fenchyl diester, which has a fenchyl ester substituent as shown in formula 2, and which was reported to be 20,000 times sweeter than sucrose. See U.S. Pat. Nos. 3,907,766; 3,959,245; M. Fujino et al., Chem. Pharm. Bull. 24:2112-2217 (1976); M. Fujino et al., Die Naturwissenschaften 60:351 (1973). ##STR3##
Liu Yin-Zeng, et. al., "Sino Amer. Symp. Chem. Nat. Prod.", 1980 (Beijing: Science Press 1982), pp. 254-256, have indicated that the intensity of the sweetness of compound 2 is modulated by the stereochemistry of the fenchyl group. Out of the four possible isomeric fenchyl alcohols, the pair exo/endo bearing an R configuration (chirality) at the C2 position reportedly gave rise to the highest sweetness intensity values (30,000 to 50,000.times.sucrose).
J. M. Janusz in EPO Appn. No. 0168112, published Jan. 15, 1986, and J. M. Gordlik in EPO Appn. No. 0168882, published Jan. 22, 1986, disclosed a series of L-aspartyl-D-phenylglycine esters having certain sweetness properties. It was found that the 2R, exo-fenchyl ester and the 2R, endofenchyl ester in this series had high sweetness intensities.
One important drawback for th applications of the fenchyl ester sweeteners like those of Liu Yin-Zeng et al. cited above, particularly in their use for soft drinks, is the release of fenchyl alcohol upon acid-catalyzed hydrolysis of the ester function. The presence of fenchyl alcohol, even at low concentrations, adversely affects the flavor characteristics of those products, due to the low taste threshold (2-5 ppm) of fenchyl alcohol and its dominant camphoraceous aroma.
The fenchyl groups of the prior art compounds are glucogenic bicycloalkyls, able to generate sweetness, but those compounds have drawbacks. Therefore, an object of the invention is the preparation of a high intensity sweetener, in which a suitable glucogenic bicycloalkyl group is attached to a dipeptide moiety in a manner which avoids the drawbacks of the prior art compounds.